The visitors, meanwhile, will be looking to bounce back from their 2-1 defeat to Freiburg on the opening matchday.
Match preview
Indeed, having been promoted as champions in the most dramatic circumstances when scoring two goals deep into injury time on the final day of last season, Heidenheim began their Bundesliga adventure with a 2-0 defeat away to Wolfsburg last weekend.
Frank Schmidt's side were caught in a bluster by Jonas Wind's early brace for the Wolves, with the Denmark striker breaking the deadlock inside the opening six minutes before doubling his tally little more than 20 minutes later.
For a team completely new to this level of football, Heidenheim reacted in a very positive manner, having more possession across the course of the encounter than Niko Kovac's side as well as generating 14 attempts and seven corners.
However, Schmidt will have his eye on the fact that they only forced their opposing goalkeeper Koen Casteels into one save, and he will be hoping for much greater penetration at Voith-Arena on Saturday.
Hoffenheim, meanwhile, began their campaign with a disappointing 2-1 defeat at home to Freiburg, with Pellegrino Matarazzo's side's defensive frailties already coming to the fore.
Attila Szalai, who was signed from Fenerbahce during the summer transfer window as part of their attempt to fix those problems at the back, had a nightmare start to his career in Germany when providing Freiburg with the lead by scoring an own goal six minutes before half-time.
Szalai's Hungarian compatriot Roland Sallai provided the visitors with a two-goal cushion on the strike of half-time, but former Liverpool defender Ozan Kabak sparked hopes of mounting a comeback when pulling one back five minutes after the break.
However, despite having 22 shots in total, Die Kraichgauer could not find a crucial equaliser. While they will not be panicking just yet - especially having finished 23 points behind Freiburg last season - they will harbor fears of being involved in another relegation battle if they do not return from Heidenheim with all three points this weekend.
Heidenheim Bundesliga form:
L
Heidenheim form (all competitions):
D
L
W
W
W
L
Hoffenheim Bundesliga form:
L
W
L
W
D
L
Hoffenheim form (all competitions):
D
W
D
L
W
L
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Team News
Heidenheim were forced to substitute Lennard Maloney and Marnon Busch during their defeat against Wolfsburg due to muscle and hip problems respectively, which could see both players out of action until after the forthcoming international break.
Elidon Qenaj remains sidelined until at least early October due to a long-term knee injury, with Schmidt likely to turn to Kevin Sessa and Omar Toure in light of their newest additions to the treatment table.
Hoffenheim, meanwhile, will travel without Wout Weghorst - who has joined on loan from Burnley for the season - due to a hip injury, while Dennis Geiger, Bambase Conte and Umut Tohumcu are all expected to miss out on the trip to Heidenheim as well.
Despite being targeted by Stuttgart as Wataru Endo's replacement after the Japan midfielder joined Liverpool, Angelo Stiller should retain his place in the visitors' engine room.
Heidenheim possible starting lineup:
Muller; Toure, Mainka, Siersleben, Fohrenbach; Dinkci, Beck, Sessa, Pick; Kleindienst, Pieringer
Hoffenheim possible starting lineup:
Baumann; Kabak, Brooks, Szalai; Kaderabek, Promel, Grillitsch, Stiller, Bulter; Bebou, Kramaric
We say: Heidenheim 0-2 Hoffenheim
Heidenheim are clearly a spirited outfit and they will carry plenty of excitement during the club's debut campaign in the Bundesliga, but scoring goals could become a major problem for them at this level.
Despite losing to Freiburg on the opening day, Hoffenheim have recruited smartly during the transfer window and they improved under Matarazzo's tutelage towards the end of last season. We can envisage them collecting all three points on Saturday.